The scavenger receptor MARCO modulates TLR-induced responses in dendritic cells.
The scavenger receptor MARCO mediates macrophage recognition and clearance of pathogens and their polyanionic ligands. However, recent studies demonstrate MARCO expression and function in dendritic cells, suggesting MARCO might serve to bridge innate and adaptive immunity. To gain additional insight...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2014-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC4121322?pdf=render |
| _version_ | 1818081560241373184 |
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| author | Haydn T Kissick Laura K Dunn Sanjukta Ghosh Morris Nechama Lester Kobzik Mohamed S Arredouani |
| author_facet | Haydn T Kissick Laura K Dunn Sanjukta Ghosh Morris Nechama Lester Kobzik Mohamed S Arredouani |
| author_sort | Haydn T Kissick |
| collection | DOAJ |
| description | The scavenger receptor MARCO mediates macrophage recognition and clearance of pathogens and their polyanionic ligands. However, recent studies demonstrate MARCO expression and function in dendritic cells, suggesting MARCO might serve to bridge innate and adaptive immunity. To gain additional insight into the role of MARCO in dendritic cell activation and function, we profiled transcriptomes of mouse splenic dendritic cells obtained from MARCO deficient mice and their wild type counterparts under resting and activating conditions. In silico analysis uncovered major alterations in gene expression in MARCO deficient dendritic cells resulting in dramatic alterations in key dendritic cell-specific pathways and functions. Specifically, changes in CD209, FCGR4 and Complement factors can have major consequences on DC-mediated innate responses. Notably, these perturbations were magnified following activation with the TLR-4 agonist lipopolysaccharide. To validate our in silico data, we challenged DC's with various agonists that recognize all mouse TLRs and assessed expression of a set of immune and inflammatory marker genes. This approach identified a differential contribution of MARCO to TLR activation and validated a major role for MARCO in mounting an inflammatory response. Together, our data demonstrate that MARCO differentially affects TLR-induced DC activation and suggest targeting of MARCO could lead to different outcomes that depend on the inflammatory context encountered by DC. |
| first_indexed | 2024-12-10T19:08:09Z |
| format | Article |
| id | doaj.art-8d0e54cf482d4eca9c7a2c922af030dc |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-10T19:08:09Z |
| publishDate | 2014-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-8d0e54cf482d4eca9c7a2c922af030dc2022-12-22T01:36:51ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0198e10414810.1371/journal.pone.0104148The scavenger receptor MARCO modulates TLR-induced responses in dendritic cells.Haydn T KissickLaura K DunnSanjukta GhoshMorris NechamaLester KobzikMohamed S ArredouaniThe scavenger receptor MARCO mediates macrophage recognition and clearance of pathogens and their polyanionic ligands. However, recent studies demonstrate MARCO expression and function in dendritic cells, suggesting MARCO might serve to bridge innate and adaptive immunity. To gain additional insight into the role of MARCO in dendritic cell activation and function, we profiled transcriptomes of mouse splenic dendritic cells obtained from MARCO deficient mice and their wild type counterparts under resting and activating conditions. In silico analysis uncovered major alterations in gene expression in MARCO deficient dendritic cells resulting in dramatic alterations in key dendritic cell-specific pathways and functions. Specifically, changes in CD209, FCGR4 and Complement factors can have major consequences on DC-mediated innate responses. Notably, these perturbations were magnified following activation with the TLR-4 agonist lipopolysaccharide. To validate our in silico data, we challenged DC's with various agonists that recognize all mouse TLRs and assessed expression of a set of immune and inflammatory marker genes. This approach identified a differential contribution of MARCO to TLR activation and validated a major role for MARCO in mounting an inflammatory response. Together, our data demonstrate that MARCO differentially affects TLR-induced DC activation and suggest targeting of MARCO could lead to different outcomes that depend on the inflammatory context encountered by DC.http://europepmc.org/articles/PMC4121322?pdf=render |
| spellingShingle | Haydn T Kissick Laura K Dunn Sanjukta Ghosh Morris Nechama Lester Kobzik Mohamed S Arredouani The scavenger receptor MARCO modulates TLR-induced responses in dendritic cells. PLoS ONE |
| title | The scavenger receptor MARCO modulates TLR-induced responses in dendritic cells. |
| title_full | The scavenger receptor MARCO modulates TLR-induced responses in dendritic cells. |
| title_fullStr | The scavenger receptor MARCO modulates TLR-induced responses in dendritic cells. |
| title_full_unstemmed | The scavenger receptor MARCO modulates TLR-induced responses in dendritic cells. |
| title_short | The scavenger receptor MARCO modulates TLR-induced responses in dendritic cells. |
| title_sort | scavenger receptor marco modulates tlr induced responses in dendritic cells |
| url | http://europepmc.org/articles/PMC4121322?pdf=render |
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